PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 8909879

Platelet-streptococcal interactions in endocarditis.

M C Herzberg
View original source ↗Export metadata ↓

Abstract

Infective endocarditis is characterized by the formation of septic masses of platelets on the surfaces of heart valves and is most commonly caused by viridans streptococci. Streptococcal virulence in endocarditis involves factors that promote infectivity and pathogenicity. Adhesins and exopolysaccharide (glycocalyx) contribute to infectivity. Although many factors may contribute to pathogenicity, the platelet aggregation-associated protein (PAAP) of Streptococcus sanguis contributes directly to the development of experimental endocarditis. PAAP is synthesized as a rhamnose-rich glycoprotein of 115 kDa and contains a collagen-like platelet-interactive domain, pro-gly-glu-gln-gly-pro-lys. Expressed on the cell wall of platelet aggregation-inducing strains (Agg+) of S. sanguis, PAAP apparently interacts with a signal-transducing receptor complex on platelets, which includes a novel 175-kDa alpha 2-integrin-associated protein and a 65-kDa collagen-binding component. From available data, the role of PAAP in the pathogenesis of experimental endocarditis may be explained by a proposed mechanistic model. On injured heart valves, PAAP first enhances platelet accumulation into a fibrin-enmeshed thrombus (vegetation), within which S. sanguis colonizes. Colonizing bacteria must resist platelet microbicidal protein (PMPR). The aggregation of platelets on the heart valve may be potentiated by an ectoATPase expressed on the surface of the S. sanguis and platelet alpha-adrenoreceptors that respond to endogenous catecholamines. The expression of PAAP may be modified during infection. Collagen is exposed on damaged heart valves; fever (heat shock) occurs during endocarditis. In response to heat shock or collagen in vitro, PAAP expression is altered. After colonization, streptococcal exotoxin(s) may cause fever. Proteases and other enzymes from streptococci and host sources may directly destroy the heart valves. When PAAP is unexpressed or neutralized with specific antibodies, experimental endocarditis runs a milder course and vegetations are smaller. The data suggest strongly, therefore, that the role of PAAP may overlap the colonization function of putative adhesins such as FimA or SsaB. Finally, PAAP also contributes to the development of the characteristic septic mural thrombus (vegetation) of infective endocarditis and the signs of valvular pathology.

Explore related subjects

Adenosine TriphosphatasesAdhesins, BacterialBacterial ProteinsBacterial ToxinsBlood PlateletsBlood ProteinsChemokinesCollagenEndocarditis, BacterialFibrinGene Expression RegulationGlycoproteinsHeart ValvesHumansIntegrinsPlatelet AggregationPolysaccharides, BacterialReceptors, Adrenergic, alphaRhamnoseSignal TransductionStreptococcal InfectionsStreptococcusStreptococcus sanguisVirulencebeta-ThromboglobulinJournal ArticleResearch Support, U.S. Gov't, P.H.S.Review

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

M C Herzberg. 1996. Platelet-streptococcal interactions in endocarditis.. https://doi.org/10.1177/10454411960070030201

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2008

Isolation and characterization of Plasmodium falciparum UAP56 homolog: evidence for the coupling of RNA binding and splicing activity by site-directed mutations.

UAP56 (U2AF65 associated protein) is a member of the DEAD-box helicase family. Helicases are essential enzymes generally involved in the metabolism of nucleic acids. The gene encoding a member of DEAD-box family was cloned and characterized from the human malaria parasite Plasmodium falciparum. PfU52 is homologous to UAP56 and contains the RNA-dependent ATPase, RNA helicase and RNA binding activities. Using the parasite extract we report that PfU52 is involved in splicing reaction. Site-directed mutagenesis studies indicate that the conserved residues glycine 181, isoleucine 182 and arginine 206 are involved in RNA binding and this activity is required for the enzymatic activities of PfU52. PfU52 is expressed in all the intraerythrocytic developmental stages of the parasite. In the present study we have reported the detailed characterization of PfU52 from P. falciparum and these results advance the knowledge regarding the function of UAP56 in general.

Adenosine Triphosphatases↗
PubMed2004

Modular organization of a Cdc6-like protein from the crenarchaeon Sulfolobus solfataricus.

In the present paper, we report that a Cdc6 (cell-division control)-like factor from the hyperthermophilic crenarchaeon Sulfolobus solfataricus (referred to as SsoCdc6-2) has a modular organization of its biological functions. A reliable model of the SsoCdc6-2 three-dimensional structure was built up, based on the significant sequence identity with the Pyrobaculum aerophylum Cdc6 (PaeCdc6), whose crystallographic structure is known. This allowed us to design two truncated forms of SsoCdc6-2: the DeltaC (residues 1-297, molecular mass 35 kDa) and the DeltaN (residues 298-400, molecular mass 11 kDa) proteins. The DeltaC protein contains the nucleotide-binding Rossmann fold and the Sensor-2 motif (Domains I and II in the PaeCdc6 structure), and retains the ability to bind and hydrolyse ATP. On the other hand, the DeltaN protein contains the C-terminal WH (winged helix)-fold (Domain III), and is able to bind DNA molecules and to inhibit the DNA helicase activity of the SsoMCM (mini-chromosome maintenance) complex, although with lesser efficiency with respect to the full-sized SsoCdc6-2. These results provide direct biochemical evidence that the Cdc6 WH-domain is responsible for DNA-binding and inhibition of MCM DNA helicase activity.

Adenosine Triphosphatases↗
PubMed2004

Intracellular trafficking of the human Wilson protein: the role of the six N-terminal metal-binding sites.

The Wilson protein (ATP7B) is a copper-transporting CPx-type ATPase defective in the copper toxicity disorder Wilson disease. In hepatocytes, ATP7B delivers copper to apo-ceruloplasmin and mediates the excretion of excess copper into bile. These distinct functions require the protein to localize at two different subcellular compartments. At the trans-Golgi network, ATP7B transports copper for incorporation into apo-ceruloplasmin. When intracellular copper levels are increased, ATP7B traffics to post-Golgi vesicles in close proximity to the canalicular membrane to facilitate biliary copper excretion. In the present study, we investigated the role of the six N-terminal MBSs (metal-binding sites) in the trafficking process. Using site-directed mutagenesis, we mutated or deleted various combinations of the MBSs and assessed the effect of these changes on the localization and trafficking of ATP7B. Results show that the MBSs required for trafficking are the same as those previously found essential for the copper transport function. Either MBS 5 or MBS 6 alone was sufficient to support the redistribution of ATP7B to vesicular compartments. The first three N-terminal motifs were not required for copper-dependent intracellular trafficking and could not functionally replace sites 4-6 when placed in the same sequence position. Furthermore, the N-terminal region encompassing MBSs 1-5 (amino acids 64-540) was not essential for trafficking, with only one MBS close to the membrane channel, necessary and sufficient to support trafficking. Our findings were similar to those obtained for the closely related ATP7A protein, suggesting similar mechanisms for trafficking between copper-transporting CPx-type ATPases.

Adenosine Triphosphatases↗